tbuckley/cabot-search huggingface dataset:
Executive Summary: International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Document
Authors: Samer Abu-Sultaneh, Narayan Prabhu Iyer, Analía Fernández, Michael Gaies, Sebastián González-Dambrauskas, Justin Christian Hotz, Martin C. J. Kneyber, Yolanda M. López-Fernández, Alexandre T. Rotta, David K. Werho, Arun Kumar Baranwal, Bronagh Blackwood, Hannah J. Craven, Martha A. Q. Curley, Sandrine Essouri, Jose Roberto Fioretto, Silvia M. M. Hartmann, Philippe Jouvet, Steven Kwasi Korang, Gerrard F. Rafferty, Padmanabhan Ramnarayan, Louise Rose, Lyvonne N. Tume, Elizabeth C. Whipple, Judith J. M. Wong, Guillaume Emeriaud, Christopher W. Mastropietro, Natalie Napolitano, Christopher J. L. Newth, Robinder G. Khemani
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Pediatric-specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients' readiness for extubation.
Science and truth during the covid-19 pandemic
Authors: P G Brindley
Journal: BMJ (2022)

of critical care medicine, ethics, anesthesiology, consultant intensive care medicine During the covid-19 pandemic, I became one of those talking heads on the TV and radio in Canada hoping to reassure communities and recommend a way forward.While doing so, I found myself in parallel discussions about two issues: what truth is and is not and what science is and is not.I may not have always succeeded in resolving these debates, but among many covid lessons, I came to appreciate how science, truth, and the scientific method are often under attack.More specifically, I came to realise that, in any debate, "truth" can be the first victim and science can be readily weaponised.
Engineering an inhibitor-resistant human CSF1R variant for microglia replacement
Authors: Jean Paul Chadarevian, Sonia I. Lombroso, Graham C. Peet, Jonathan Hasselmann, Christina Tu, Dave E. Marzan, Joia Capocchi, Freddy S. Purnell, Kelsey M. Nemec, Alina Lahian, Adrian Escobar, Whitney England, Sai Chaluvadi, Carleigh A. O’Brien, Fazeela Yaqoob, William H. Aisenberg, Matias Porras-Paniagua, Mariko L. Bennett, Hayk Davtyan, Robert C. Spitale, Mathew Blurton-Jones, F. Chris Bennett
Journal: The Journal of Experimental Medicine (2022)

Hematopoietic stem cell transplantation (HSCT) can replace endogenous microglia with circulation-derived macrophages but has high mortality. To mitigate the risks of HSCT and expand the potential for microglia replacement, we engineered an inhibitor-resistant CSF1R that enables robust microglia replacement. A glycine to alanine substitution at position 795 of human CSF1R (G795A) confers resistance to multiple CSF1R inhibitors, including PLX3397 and PLX5622. Biochemical and cell-based assays show no discernable gain or loss of function. G795A- but not wildtype-CSF1R expressing macrophages efficiently engraft the brain of PLX3397-treated mice and persist after cessation of inhibitor treatment. To gauge translational potential, we CRISPR engineered human-induced pluripotent stem cell-derived microglia (iMG) to express G795A. Xenotransplantation studies demonstrate that G795A-iMG exhibit nearly identical gene expression to wildtype iMG, respond to inflammatory stimuli, and progressively expand in the presence of PLX3397, replacing endogenous microglia to fully occupy the brain. In sum, we engineered a human CSF1R variant that enables nontoxic, cell type, and tissue-specific replacement of microglia.
Age-related liver endothelial zonation triggers steatohepatitis by inactivating pericentral endothelium-derived C-kit
Authors: Juan-Li Duan, Jing-Jing Liu, Bai Ruan, Jian Ding, Zhi-Qiang Fang, Hao Xu, Ping Song, Chen Xu, Zhi-Wen Li, Wei Du, Ming Xu, Yu-Wei Ling, Fei He, Lin Wang
Journal: Nature Aging (2022)
Distinct fibroblast progenitor subpopulation expedites regenerative mucosal healing by immunomodulation
Authors: Kang I. Ko, Brett P. DerGarabedian, Zhaoxu Chen, Rahul Debnath, Annette Ko, Brittany N. Link, Jonathan M. Korostoff, Dana T. Graves
Journal: The Journal of Experimental Medicine (2022)

Injuries that heal by fibrosis can compromise organ function and increase patient morbidity. The oral mucosal barrier has a high regenerative capacity with minimal scarring, but the cellular mechanisms remain elusive. Here, we identify distinct postnatal paired-related homeobox-1+ (Prx1+) cells as a critical fibroblast subpopulation that expedites mucosal healing by facilitating early immune response. Using transplantation and genetic ablation model in mice, we show that oral mucosa enriched with Prx1+ cells heals faster than those that lack Prx1+ cells. Lineage tracing and scRNA-seq reveal that Prx1+ fibroblasts exhibit progenitor signatures in physiologic and injured conditions. Mechanistically, Prx1+ progenitors accelerate wound healing by differentiating into immunomodulatory SCA1+ fibroblasts, which prime macrophage recruitment through CCL2 as a key part of pro-wound healing response. Furthermore, human Prx1+ fibroblasts share similar gene and spatial profiles compared to their murine counterpart. Thus, our data suggest that Prx1+ fibroblasts may provide a valuable source in regenerative procedures for the treatment of corneal wounds and enteropathic fibrosis.
Transposable elements and Alzheimer’s disease pathogenesis
Authors: Teresa H. Evering, Jez L. Marston, Li Gan, Douglas F. Nixon
Journal: Trends in Neurosciences (2022)

Alzheimer's disease (AD) is characterized by the pathological accumulation of amyloid β (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau. Microglia and astrocytes respond to the abnormal presence of tau protein with induced transposable element (TE) transcription. In this Forum, we discuss new data that link dysregulated TE expression to AD pathogenesis.
The landscape of expression and alternative splicing variation across human traits
Authors: Raquel García-Pérez, Jose Miguel Ramirez, Aida Ripoll-Cladellas, Ruben Chazarra-Gil, Winona Oliveros, Oleksandra Soldatkina, Mattia Bosio, Paul Joris Rognon, Salvador Capella-Gutierrez, Miquel Calvo, Ferran Reverter, Roderic Guigó, François Aguet, Pedro G. Ferreira, Kristin G. Ardlie, Marta Melé
Journal: Cell Genomics (2022)

Understanding the consequences of individual transcriptome variation is fundamental to deciphering human biology and disease. We implement a statistical framework to quantify the contributions of 21 individual traits as drivers of gene expression and alternative splicing variation across 46 human tissues and 781 individuals from the Genotype-Tissue Expression project. We demonstrate that ancestry, sex, age, and BMI make additive and tissue-specific contributions to expression variability, whereas interactions are rare. Variation in splicing is dominated by ancestry and is under genetic control in most tissues, with ribosomal proteins showing a strong enrichment of tissue-shared splicing events. Our analyses reveal a systemic contribution of types 1 and 2 diabetes to tissue transcriptome variation with the strongest signal in the nerve, where histopathology image analysis identifies novel genes related to diabetic neuropathy. Our multi-tissue and multi-trait approach provides an extensive characterization of the main drivers of human transcriptome variation in health and disease.
Tubular-specific expression of HIV protein Vpr leads to severe tubulointerstitial damage accompanied by progressive fibrosis and cystic development
Authors: Yuqiang Chen, Ya Chen, Jia Fu, Zeguo Sun, Huilin Li, Wenzhen Xiao, Jing E, Benjamin Y. Lo, Niansong Wang, Weijia Zhang, Mary E. Klotman, Paul E. Klotman, Jeffrey B. Kopp, Vivette D. D’Agati, John Cijiang He, Kyung Lee
Journal: Kidney International (2022)
Effects of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on substrate metabolism in prediabetic insulin resistant individuals: A randomized, double-blind crossover trial
Authors: Anna Veelen, Charlotte Andriessen, Yvo Op den Kamp, Edmundo Erazo-Tapia, Marlies de Ligt, Julian Mevenkamp, Johanna A Jörgensen, Esther Moonen-Kornips, Gert Schaart, Russell Esterline, Bas Havekes, Jan Oscarsson, Vera B Schrauwen-Hinderling, Esther Phielix, Patrick Schrauwen
Journal: Metabolism (2022)
2D-CuPd nanozyme overcome tamoxifen resistance in breast cancer by regulating the PI3K/AKT/mTOR pathway
Authors: Wenwei Jiang, Suqin Zhong, Ziying Chen, Jieying Qian, Xiaowan Huang, Hao Zhang, Longping Wen, Yunjiao Zhang, Guangyu Yao
Journal: Biomaterials (2022)
Decreased Lacrimation in Amyotrophic Lateral Sclerosis
Authors: Reuben Copperman
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Decreased lacrimation is not usually regarded as a feature of amyotrophic lateral sclerosis. In the course of treating ten such patients over the last two years, decreasedlacrimation as measured by the Schirmer test was observed. Since this is a devastating disease of unknown etiology, it is to be hoped that decreased lacrimation will be confirmed by others and explored as a new lead. The Schirmer tear test is performed by placing the tip of a strip of filter paper on the conjunctiva of the lower lid at the juncture of the outer and middle third of the lid. The patient closes his eyes lightly and after five minutes the length of filter paper wet by tears is recorded. Less than 15 mm of wetting is regarded as evidence of decreased tear production. Normal eyes can wet the entire 35-mm length in less than five minutes.
Retinitis Pigmentosa
Authors: Michael F. Marmor, Gustavo Aguirre, Geoffrey Arden, Eliot Berson, David G. Birch, Joann A. Boughman, Ronald Carr, Gian E. Chatrian, Monte Del Monte, John Dowling, Jay Enoch, Gerald A. Fishman, Ann B. Fulton, Charles A. Garcia, Peter Gouras, John Heckenlively, Dan-Ning Hu, Richard A. Lewis, Gunter Niemeyer, John A. Parker, Ido Perlman, Harris Ripps, Michael A. Sandberg, Irwin Siegel, Richard G. Weleber, Mitchell L. Wolf, Lezheng Wu, Rockefeller S.L. Young
Journal: Ophthalmology (1983)
Screening for Prostate Cancer
Authors: Murray D. Krahn
Journal: JAMA (1994)

<h3>Objective.</h3> —To determine the clinical and economic effects of screening for prostate cancer with prostate-specific antigen (PSA), transrectal ultrasound (TRUS), and digital rectal examination (DRE). <h3>Design.</h3> —Decision analytic cost-utility analysis comparing four screening strategies with a strategy of not screening. We assumed that the cancer detection rate and stage distribution were predicted by each combination of tests and that localized cancer was treated with radical prostatectomy. For each strategy, we calculated life expectancy, quality-adjusted life expectancy (QALE), and cost-utility ratios for unselected and high-prevalence populations. <h3>Data.</h3> —Probabilities and rates for clinical events were gathered from published data. We assessed utilities by the time—trade-off method using urologists, radiation oncologists, and internists as subjects. The Clinical Cost Manager at the New England Medical Center provided cost data. <h3>Results.</h3> —In unselected men between the ages of 50 and 70 years, screening with PSA or TRUS prolonged unadjusted life expectancy but diminished QALE. Screening with DRE alone yielded no reduction in mortality at any age. All programs increased costs. Results were sensitive only to assumptions about the efficacy of treatment. In high-prevalence populations, screening produced a similar pattern: gains in unadjusted life expectancy, losses in QALE, and increased costs. <h3>Conclusions.</h3> —Our analysis does not support using PSA, TRUS, or DRE to screen asymptomatic men for prostatic cancer. Screening may result in poorer health outcomes and will increase costs dramatically. Assessment of comorbidity, risk attitude, and valuation of sexual function may identify individuals who will benefit from screening, but selecting high-prevalence populations will not improve the benefit of screening. (<i>JAMA</i>. 1994;272:773-780)
Polyvinyl Chloride Toxicity in Fires
Authors: Robert F. Dyer
Journal: JAMA (1976)

Polyvinyl chloride, of all the plastic polymers, has been implicated primarily in causing the most serious problem in fire fighting today because it releases hydrogen chloride gas when burning. One hundred seventy fire fighters who experienced symptoms from its toxicity have been studied from 1970 to 1975. One died. (<i>JAMA</i>235:393-397, 1976)
Decreased Brain Choline Uptake in Older Adults
Authors: Bruce M. Cohen
Journal: JAMA (1995)

<h3>Objective.</h3> —To test the hypothesis that uptake of circulating choline into the brain decreases with age, because alterations in metabolism of choline may be a factor contributing to age-related degenerative changes in the brain. <h3>Design.</h3> —Cohort comparison in younger and older adults. <h3>Participants.</h3> —Subjects were chosen consecutively from lists of healthy volunteers screened by medical and psychiatric interviews and laboratory tests. Younger adults (n=12) were between the ages of 20 and 40 years (mean age, 32 years), and older adults (n=16) were between the ages of 60 and 85 years (mean age, 73 years). <h3>Interventions.</h3> —After fasting overnight, subjects received choline, as the bitartrate, to yield free choline equal to 50 mg/kg of body weight. Blood was drawn for determination of plasma choline concentration by high-performance liquid chromatography, and proton magnetic resonance spectroscopy (<sup>1</sup>H-MRS) was performed to determine the relative concentration of cytosolic choline—containing compounds in the brain at baseline and after ingestion of choline. <h3>Main Outcome Measures.</h3> —Plasma choline and cytosolic choline—containing compounds in the brain, estimated as the ratio of the choline resonance to the creatine resonance on<sup>1</sup>H-MRS scans of the basal ganglia, were compared following blinded analyses of data from subject cohorts studied at baseline and 3 hours after choline ingestion. <h3>Results.</h3> —Levels of plasma choline and cytosolic choline—containing compounds in brain were similar at baseline in younger and older subjects. Following ingestion of choline, plasma choline concentration increased by similar proportions (76% and 80%) in both younger and older subjects. Brain cytosolic choline— containing compounds increased substantially in younger subjects (mean increase, 60%;<i>P</i>&lt;.001 vs baseline). Older subjects showed a much smaller increase in brain choline—containing compounds (mean, 16%;<i>P</i>&lt;.001 vs the increase in younger subjects). <h3>Conclusion.</h3> —Uptake of circulating choline into the brain decreases with age. Given the key role of choline in neuronal structure and function, this change may be a contributing factor in onset in late life of neurodegenerative, particularly dementing, illnesses in which cholinergic neurons show particular susceptibility to loss. (<i>JAMA</i>. 1995;274:902-907)
A compilation answering 50 questions on monkeypox virus and the current monkeypox outbreak
Authors: Beatriz Cabanillas, Giuseppe Murdaca, Amir Guemari, Maria Jose Torres, Ahmet Kursat Azkur, Emel Aksoy, Joana Vitte, Leticia de las Vecillas, Mattia Giovannini, Ruben Fernández‐Santamaria, Riccardo Castagnoli, Andrea Orsi, Rosa Amato, Irene Giberti, Alba Català, Dominika Ambrozej, Bianca Schaub, Gerdien A. Tramper‐Stranders, Natalija Novak, Kari C. Nadeau, Ioana Agache, Mubeccel Akdis, Cezmi A. Akdis
Journal: Allergy (2023)

The current monkeypox disease (MPX) outbreak constitutes a new threat and challenge for our society. With more than 55,000 confirmed cases in 103 countries, World Health Organization declared the ongoing MPX outbreak a Public Health Emergency of International Concern (PHEIC) on July 23, 2022. The current MPX outbreak is the largest, most widespread, and most serious since the diagnosis of the first case of MPX in 1970 in the Democratic Republic of the Congo (DRC), a country where MPX is an endemic disease. Throughout history, there have only been sporadic and self-limiting outbreaks of MPX outside Africa, with a total of 58 cases described from 2003 to 2021. This figure contrasts with the current outbreak of 2022, in which more than 55,000 cases have been confirmed in just 4 months. MPX is, in most cases, self-limiting; however, severe clinical manifestations and complications have been reported. Complications are usually related to the extent of virus exposure and patient health status, generally affecting children, pregnant women, and immunocompromised patients. The expansive nature of the current outbreak leaves many questions that the scientific community should investigate and answer in order to understand this phenomenon better and prevent new threats in the future. In this review, 50 questions regarding monkeypox virus (MPXV) and the current MPX outbreak were answered in order to provide the most updated scientific information and to explore the potential causes and consequences of this new health threat.
Pre-treatment of oncolytic reovirus improves tumor accumulation and intratumoral distribution of PEG-liposomes
Authors: Maho Eguchi, Seiya Hirata, Ikuho Ishigami, Naomi Shuwari, Ryosuke Ono, Masashi Tachibana, Masato Tanuma, Atsushi Kasai, Hitoshi Hashimoto, Ken-ichi Ogawara, Hiroyuki Mizuguchi, Fuminori Sakurai
Journal: Journal of Controlled Release (2023)
Contribution of genetic variants associated with primary immunodeficiencies to childhood-onset systemic lupus erythematous
Authors: Chao-Yi Wu, Wen-Lang Fan, Huang-Yu Yang, Pi-Shuang Chu, Pei-Chun Liao, Li-Chen Chen, Tsung-Chieh Yao, Kuo-Wei Yeh, Liang-Shiou Ou, Syh-Jae Lin, Wen-I Lee, Jing-Long Huang
Journal: Journal of Allergy and Clinical Immunology (2022)
Generation of bioactive MSC-EVs for bone tissue regeneration by tauroursodeoxycholic acid treatment
Authors: Kyung-Yup Cha, Woongjin Cho, Sunghyun Park, Jinsung Ahn, Hyoeun Park, Inho Baek, Minju Lee, Sunjun Lee, Yoshie Arai, Soo-Hong Lee
Journal: Journal of Controlled Release (2023)
New vegetable-waste biomaterials by Lupin albus L. as cellular scaffolds for applications in biomedicine and food
Authors: Silvia Buonvino, Matteo Ciocci, Francesca Nanni, Ilaria Cacciotti, Sonia Melino
Journal: Biomaterials (2022)

The reprocessing of vegetal-waste represents a new research field in order to design novel biomaterials for potential biomedical applications and in food industry. Here we obtained a biomaterial from Lupinus albus L. hull (LH) that was characterized micro-structurally by scanning electron microscopy and for its antimicrobial and scaffolding properties. A good adhesion and proliferation of human mesenchymal stem cells (hMSCs) seeded on LH scaffold were observed. Thanks to its high content of cellulose and beneficial phytochemical substances, LH and its derivatives can represent an available source for fabrication of biocompatible and bioactive scaffolds. Therefore, a reprocessing protocol of LH was optimized for producing a new LH bioplastic named BPLH. This new biomaterial was characterized by chemico-physical analyses. The water uptake, degradability and antimicrobial properties of BPLH were evaluated, as well as the mechanical properties. A good adhesion and proliferation of both fibroblasts and hMSCs on BPLH were observed over 2 weeks, and immunofluorescence analysis of hMSCs after 3 weeks indicates an initial commitment toward muscle differentiation. Our work represents a new approach toward the recovery and valorization of the vegetal waste showing the remarkable properties of LH and BPLH as cellular waste-based scaffold with potential applications in cell-based food field as well as in medicine for topical patches in wound healing and bedsores treatment.
How does particulate air pollution affect barrier functions and inflammatory activity of lung vascular endothelium?
Authors: Krzysztof Olesiejuk, Maciej Chałubiński
Journal: Allergy (2023)

Both particulate matter and gaseous components of air pollution have already been shown to increase cardiovascular mortality in numerous studies. It is, however, important to note that on their way to the bloodstream the polluting agents pass the lung barrier. Inside the alveoli, particles of approximately 0.4-1 μm are most efficiently deposited and commonly undergo phagocytosis by lung macrophages. Not only the soluble agents, but also particles fine enough to leave the alveoli enter the bloodstream in this finite part of the endothelium, reaching thus higher concentrations in close proximity of the alveoli and endothelium. Additionally, deposits of particulate matter linger in direct proximity of the endothelial cells and may induce inflammation, immune responses, and influence endothelial barrier dysfunction thus increasing PM bioavailability in positive feedback. The presented discussion provides an overview of possible components of indoor PM and how endothelium is thus influenced, with emphasis on lung vascular endothelium and clinical perspectives.
N‐terminal <scp>pro‐brain</scp> natriuretic peptide is a prognostic marker for response to intensive chemotherapy, early death, and overall survival in acute myeloid leukemia
Authors: Irene Graf, Georg Greiner, Rodrig Marculescu, Karoline V. Gleixner, Susanne Herndlhofer, Gabriele Stefanzl, Paul Knoebl, Ulrich Jäger, Alexander Hauswirth, Ilse Schwarzinger, Renate Thalhammer, Michael Kundi, Gregor Hoermann, Gerlinde Mitterbauer‐Hohendanner, Peter Valent, Wolfgang R. Sperr
Journal: American Journal of Hematology (2023)

Abstract Patient‐related factors are of prognostic importance in acute myeloid leukemia (AML). Likewise, cardiac disorders may limit the tolerance of intensive therapy. Little is known about the prognostic value of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). We analyzed NT‐proBNP levels at diagnosis in 312 AML patients (median age: 61 years; range 17–89 years) treated with 3 + 7‐based induction‐chemotherapy and consolidation with up to four cycles of intermediate or high‐dose ARA‐C. NT‐proBNP levels were elevated in 199 patients (63.8%), normal (0–125 pg/ml) in 113 (36.2%), and highly elevated (&gt;2000 pg/ml) in 20 patients (6.4%). Median NT‐proBNP levels differed significantly among patients with complete remission (153.3 pg/ml), no remission (225.9 pg/ml), or early death (735.5 pg/ml) ( p = .002). In multivariate analysis, NT‐proBNP, age, and the 2009 European LeukemiaNet (ELN‐2009) classification were independent predictors of outcome after induction chemotherapy. Overall survival (OS) differed significantly between patients with normal, moderately elevated, and highly elevated NT‐proBNP ( p &lt; .001). These differences were observed in all patients and in patients &lt;60 years but not in those ≥60 years. In multivariate analysis, NT‐proBNP, age, and ELN‐2009 remained independent prognostic variables for OS ( p &lt; .01). Together, NT‐proBNP is an independent prognostic factor indicating the risk of induction failure, early death, and reduced OS in patients with AML.